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Control of metamorphic timing by unliganded thyroid hormone receptor through the recruitment of histone deacetylase‐containing corepressor complexes during frog development
Author(s) -
Shi YunBo
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1046.1
Subject(s) - corepressor , biology , metamorphosis , thyroid hormone receptor , nuclear receptor , histone deacetylase , histone , psychological repression , demethylase , microbiology and biotechnology , medicine , gene , endocrinology , hormone , transcription factor , gene expression , genetics , botany , larva
Thyroid hormone (T3) is important for vertebrate development and adult organ function. We have been using amphibian metamorphosis as a model for studying the role of T3 receptor (TR) in vertebrate development. We previously proposed a dual function model for TR during development. That is, during premetamorphosis, unliganded TR recruits corepressor complexes to repress gene expression and prevent premature metamorphic transformation, while during metamorphosis, T3‐bound TR recruits coactivators to activate transcription and initiate metamorphosis. Here we have investigated the role of unliganded TR during frog development. We had previously shown that unliganded TR recruits histone deacetylase complexes containing TR‐binding corepressors N‐CoR/SMRT. Thus, we designed a dominant negative form of N‐CoR (dnN‐CoR) containing only the TR‐interacting domain of N‐CoR. We overexpressed dnN‐CoR under the control of a heat shock inducible promoter in tadpoles through transgenesis. RT‐PCR revealed significant derepression of T3‐response genes in transgenic animals. More importantly, transgenic tadpoles developed faster than wild type siblings, with an acceleration of as much as 7 days out of the 30‐day experiment. These data thus demonstrate a role of unliganded TR‐induced gene repression in controlling metamorphic timing by recruiting histone deacetylase‐containing corepressor complexes.